A general strategy for C(sp3)-H functionalization with nucleophiles using methyl radical as a hydrogen atom abstractor

When carbon-based units are functionalized in photoredox catalysis, electrophilic coupling partners are often used, such that the polarities of the two fragments are appropriately matched. Here the authors show a generalized methodology to instead use nucleophilic coupling partners, which are cheaper and often simpler, via successive hydrogen atom transfer and oxidative radical-polar crossover. Photoredox catalysis has provided many approaches to C(sp(3))-H functionalization that enable selective oxidation and C(sp(3))-C bond formation via the intermediacy of a carbon-centered radical. While highly enabling, functionalization of the carbon-centered radical is largely mediated by electrophilic reagents. Notably, nucleophilic reagents represent an abundant and practical reagent class, motivating the interest in developing a general C(sp(3))-H functionalization strategy with nucleophiles. Here we describe a strategy that transforms C(sp(3))-H bonds into carbocations via sequential hydrogen atom transfer (HAT) and oxidative radical-polar crossover. The resulting carbocation is functionalized by a variety of nucleophiles-including halides, water, alcohols, thiols, an electron-rich arene, and an azide-to effect diverse bond formations. Mechanistic studies indicate that HAT is mediated by methyl radical-a previously unexplored HAT agent with differing polarity to many of those used in photoredox catalysis-enabling new site-selectivity for late-stage C(sp(3))-H functionalization.